The George M. O'Brien Urology Research Center at the University of Pennsylvania entitled "Bladder Wall Remodeling in LUTS " has three key elements: 1) the laboratories of five principal investigators and their Co-Is that bring expertise in molecular biology, cellular biology, neuroscience, biochemistry, physiology, pharmacology, and pathology;2) an Administrative Core (Core A) to provide administrative and fiscal oversight, quality control for the research within individual projects and coordination of the research and interactions in the Center, 3) a Bladder Tissue Core (Core B) to serve as resource for smooth muscle tissue of the LUTS from rabbits, rats, and mice (normal and obstructed bladders and urethra). In addition, we have Educational &Enrichment and Pilot and Feasibility (P&F) programs to attract young investigators and established investigators working in other biomedical areas to urologic research. The four projects are: 1) "Social-stress-induced urinary dysfunction: A model of dysfunctional voiding" from Rita Valentino, 2) "Bladder wall remodeling following alteration of urothelial structure" from Pam Howard (in collaboration with Dr. Tung-Tien Sun at NYU), 3) entitled "Mechanism for obstruction-induced detrusor remodeling: Role of hypoxia &stretch" from Samuel K. Chacko, and 4) entitled "Extracellular Matrix Changes in Response to Obstruction" from Edward Macarak. In addition, we have two P&F projects, one from Shaohua Chang entitled "Urethral function in females: A Role for estrogen" and one from Gina Northington entitled "The effect of PBOO and estrogen on detrusor smooth muscle in female rabbits." The focus of this O'Brien Program is to elucidate the mechanism for social stress- and PBOO-induced functional and structural changes in the bladder wall leading to LUTS. These studies will provide a useful model for dysfunctional voiding in children and elucidate the molecular basis for urinary dysfunction in menopausal women and aging men with BPHinduced PBOO. A better understanding of the basic mechanisms for alteration of the structure and function of the bladder wall and urethra in LUTS would help to develop therapeutic strategies targeting altered molecular events that cause altered function in the lower urinary tract.